Genomic deletions and rearrangements in monkeypox virus from the 2022 outbreak, USA

Abstract

Genomic surveillance of monkeypox virus (MPXV) during the 2022 outbreak has been mainly focused on single nucleotide polymorphism (SNP) changes. DNA viruses, including MPXV, have a lower SNP mutation rate than RNA viruses due to higher fidelity replication machinery. We identified a large genomic rearrangement in a MPXV sequence from a 2022 case in the state of Minnesota (MN), USA, from an abnormal, uneven MPXV read mapping coverage profile in whole-genome sequencing (WGS) data. We further screened WGS data of 206 U.S. MPXV samples and found seven (3.4 percent) sequenced genomes contained similar abnormal read coverage profiles that suggested putative large deletions or genomic rearrangements. Here, we present three MPXV genomes containing deletions ranging from 2.3 to 15 kb and four genomes containing more complex rearrangements. Five genomic changes were each only seen in one sample, but two sequences from linked cases shared an identical 2.3 kb deletion in the 3’ terminal region. All samples were positive using VAC1 and Clade II (formerly West African)-specific MPXV diagnostic tests; however, large deletions and genomic rearrangements like the ones reported here have the potential to result in viruses in which the target of a PCR diagnostic test is deleted. The emergence of genomic rearrangements during the outbreak may have public health implications and highlight the importance of continued genomic surveillance.

Sequencing of monkeypox virus from infected patients reveals viral genomes with APOBEC3‐like editing, gene inactivation, and bacterial agents of skin superinfection

“…This is congruent with substantial differences in the sets of mutations reported in B.1 genomes in several studies and according to the B.1 sublineages 5,7,13,31,39‐41,42,48,52 . Aside this substantial genetic diversity between B.1 MPXV genomes due to substitutions and short indels, gene duplications, deletions, rearrangements and recombinations have been reported to shape the genomes of MPXV involved in the 2022 outbreak, 13,49,50 in congruence with what has been previously described for the evolution of MPXV 1,51 …”

Monkeypox Infection 2022: An Updated Narrative Review Focusing on the Neonatal and Pediatric Population

“…Although in the past MPV underwent few mutations, overtime, as happens for other DNA viruses, [ 15 , 16 ], more mutations are now increasingly being reported. These recent mutations are different from those already known previously, likely reflecting the fact that the virus is now able to survive in the population more easily [ 4 , 16 ].…”

Development of an amplicon-based sequencing approach in response to the global emergence of human monkeypox virus

“…This warrants careful interpretation of sequencing results in these genome regions. Lastly, Orthopox viruses are known to have genomic rearrangements (translocations, duplications, and inversions) especially in the inverted terminal repeats [23], which may not be well identified by amplicon-based sequencing. Although we recently identified a 600 bp deletion in the inverted terminal repeats that affects commonly used real-time PCR assays [24], amplicon-based sequencing may not be able to identify other genomic rearrangements that may have epidemiological or clinical significance.…”